Study Of Vitamin D Level In Critically Ill Children.
Mohammed Z. Neel, MD., Shaheen A.Dabour, MD., Ghada S. Abdelmotaleb, MD., Yasser
M.Ismail*, MD. and Shaimaa Reda, MSc.
Pediatrics and Clinical pathology * departments, Faculty of Medicine, Benha University.
Abstract:
Objective: To assess prevalence of 25 (OH)D deficiency in critically ill
children , possible risk factors and whether it is associated with increased
mortality and hospital stay
Patients and Methods: This is cross sectional study of 25(OH) D levels
conducted on 48 patients within the first 24 hours of PICU admission.
Analysis of the demographic data and PRISM III score between the deficient
and sufficient group in the PICU. Vitamin D deficiency was defined as
levels from 30 to 75 nmol/L and serious deficiency< 30 nmol/L.
Results: Median of 25(OH)D level was 63.7 nmol/L in the whole study
group of PICU patients. The prevalence of 25(OH)D < 30 nmol/L was
33.3%, patients with vitamin D deficiency had higher age. Median age in
severely deficient patients was 2.25 years with p value (<0.05). PRISM III
score, mortality and duration of hospital stay were not associated with
vitamin D deficiency, although high PELOD score was associated with
vitamin D deficiency. Median of 25(OH)D level at the time of discharge was
59.1 nmol/L which is not affected by time of mechanical ventilation or
PICU length of stay.
Conclusions: Hypovitaminosis D incidence was high in PICU patients
especially those with older age, no vitamin D supplementation or sun
exposure. Hypovitaminosis D was not associated with higher PRISM III
scores or mortality. The level of vitamin D at the time of discharge is
significantly decreased in comparison with its level on admission.
Key words: PICU, 25(OH)D, PRISM III score, mortality.
Introduction:
Vitamin D, a nutrient derived from both diet and sunlight, has been
increasingly recognized as pivotal to good health. A pleiotropic hormone,
vitamin D has been increasingly implicated in the proper functioning of
multiple organs; its deficiency is associated with cardiovascular disease,
asthma, multiple sclerosis, diabetes, acute lower respiratory infection
(ALRI) and cancer (1).
The level of 25(OH)D needed for adequate immune and
cardiovascular function is unclear. Vitamin D deficiency has been associated
with increased viral respiratory infections and sepsis in children and adults
(Ginde et al., 2011). This could be because 25(OH)D influences production
of cathelicidin hCAP-18, an anti-microbial peptide (3).
Aim of the work:
The aim of this study is to determine the prevalence of vitamin D
deficiency among critically ill children admitted to pediatric intensive care
unit , Benha University hospitals. Studying the risk factors for vitamin D
deficiency and exploring its relationships with the clinical outcomes.
Patients and method:
This study was performed in Pediatric Intensive Care Unit, Pediatric
Department, Benha University Hospitals. We studied all patients admitted
to Pediatric Intensive Care unit during the period from March 2014 to
August 2014 included the age groups from 1 month to 18 years of either
sex. The number of included cases was 48 patients.
Eligibility criteria:
1. Age of the patients from one month to 18 years.
2. Estimated PICU stay > 48 hrs (excluding short term monitoring
patients).
Exclusion criteria:
1. Patients with known
hypothalamic disease.
or
suspected
adrenal,
pituitary
or
2. Patients who received systemic steroids for >10 days in the
previous month or more than 1 dose of systemic steroids within 24
hours of admission.
3. Patients who transferred from another ICU.
4. Patients after trauma.
All patients were subjected to:
 Full history taking at the time of admission which included age,
sex, residence, order among siblings, onset of the illness either
acute or acute on top of chronic illness.
 History was taken about child’s background, sun exposure, intake
of vitamin D supplements and type of milk.
 Examination at the time of admission including all body systems.
Patients’ height and weight were taken and its percentiles for age
were checked according to the Egyptian growth curves (2002).
 The severity of illness in the first 24 hours was assessed as defined
by Pediatric Risk of Mortality III (PRISM-III) score (4) and
Pediatric Logistic Organ Dysfunction (PELOD) score (5).
 Number of organ system failure was detected on
admission.
1st
day of
 Presence or absence of sepsis & its degree (if present) were
identified according to International Pediatric sepsis consensus
conference (6) & (7). Our classification of sepsis syndromes where
mainly according to Proulx classification except for the last grade
we took it from Goldstien classification.
 During admission in our PICU the cases were followed up for:
1. Catecholamine administration: Maximum level of vasopressor use
during PICU stay will be assessed by using the Sequential Organ
Failure Assessment cardiovascular (CV-SOFA) score (8) with 0–1:
no vasopressors, 2: dopamine <5 mcg/kg/min, 3: dopamine 5 to 15
mcg/kg/min or norepinephrine/ epinephrine <0.1 mcg/kg/min, and
4: dopamine >15 mcg/kg/min or norepinephrine/epinephrine
>0.1mcg/kg/min.
2. Mechanical ventilation duration if the patient was ventilated.
3. PICU length of stay.
4. The outcome.
Before withdrawing the samples an informed consents were taken
from the parents.
 The following laboratory tests were performed:
 Serum Ca
 Serum Phosphorus
 Serum ALT, AST and ALP
 Serum Urea and Creatinine
 Serum 25(OH) vitamin D
Previous parameters were measured using Biosystem A15 Autoanalyzer by the appropriate chemical principles.
 Sample collection and storage for Serum 25(OH) vitamin D
Blood samples for serum 25(OH)D were obtained within the first 24
hours of PICU admission and at the time of discharge.
Under sterile aseptic techniques 3 ml of venous blood were withdrawn in
a sterile test tube. All blood samples were put in a refrigerator at 4 ˚C for
the night then centrifuged for 10 minutes at 1000-3000- rpm. The
supernatant was stored at -20˚C until analysis by ELISA Kit
MyBiosource USA.
Results
Patients were categorized into three groups according to 25(OH)
VitaminD level, adequate (>75nmol\L), insufficient (30-75nmol\L) and
seriously deficient (<30nmol\L).There were 19 patients(39.6%) with
adequate vitamin D level, 13 patients (27.1%) with insufficient vitamin D
level and 16(33.3%) with seriously deficient vitamin D level.
seriously
deficient
33.3%
adequate
39.6%
Figure (1)
Distribution of
study population
according to
Vitamin D level
insufficien
t
27.1%
Table (1): Vitamin D level in different groups as regard age.
Demographic
characteristic
Age
Variables
Median
Minimum
Maximum
Mean
r
25OH vitamin D grouped
(number & percent)
Adequate
(>75nmol/L)
(30-75 nmol/L)
1.1
0.25
4
1.5
0.67
0.17
5
0.97
Seriously
deficient
(<30nmol/L)
2.25
0.17
12
4
-0.15
P-Value
<0.05*
>0.05
This table shows that there was statistically significant difference in vitamin
D level among the adequate, insufficient and seriously deficient groups as
regard to age.
Table (2): Clinical characteristics of study population according to vitamin D level.
Variables
Acute or acute on
top of chronic illness
Type of milk
supplementation
Vitamin D
supplementation
Sun exposure
CV SOFA score
PRISM III score
PELOD score
Weight Percentile
Height percentile
Sepsis or not
Manifestations of
rickets
Mechanically
ventilated or not
Acute
Acute on top of
chronic
artificial
Breast
No
Yes
Good
Improper
No
Median
Minimum
Maximum
Mean
Median
Minimum
Maximum
Mean
Median
Minimum
Maximum
Mean
r
Above 25th
Below 25th
Above 25th
Below 25th
No
yes
Absent
Present
No
Yes
25OH vitamin D grouped
(number & percent)
Adequate
Insufficient
Seriously
(>75nmol/L)
(30deficient
75nmol/L)
(<30nmol/L
)
8 (42.1%)
9(69.2%)
9(56.2%)
11(57.9%)
4(30.8%)
7(43.8%)
4(21.1%)
15(78.9%)
10(52.6%)
9(47.4%)
11(57.9%)
5(26.3%)
3(15.8%)
0
0
4
0.8
6
1
22
8.7
10
0
31
9.2
4(21.1%)
15(78.9%)
4(21.1%)
15(78.9%)
5(26.3%)
14(73.7%)
14(73.7%)
5(26.3%)
11(57.9%)
8(42.1%)
2(15.4%)
11(84.6%)
11(84.6%)
2(15.4%)
3(23.1%)
4(30.8%)
6(46.2%)
0
0
4
1.1
8
2
24
9.9
11
0
32
10.9
0(0%)
16(100%)
14(87.5%)
2(12.5%)
1(6.2%)
10(62.5%)
5(31.2%)
0
0
4
0.75
9.5
3
19
10.1
20
0
31
16.9
-0.3
6(46.2%)
7(53.8%)
6(46.2%)
7(53.8%)
3(23.1%)
10(76.9%)
9(68.2%)
4(30.8%)
7(53.8%)
6(46.2%)
6(37.5%)
10(62.5%)
6(37.5%)
10(62.5%)
3(18.8%)
13(81.2%)
13(81.2%)
3(18.8%)
11(68.8%)
5(31.2%)
P-value
>0.05
>0.05
<0.05*
<0.05*
>0.05
>0.05
<0.05*
<0.05*
>0.05
>0.05
>0.05
>0.05
>0.05
*P-value < 0.05 is considered significant, r =Spearman's rho correlations.
This table shows that there was a statistically significant difference among
adequate, insufficient and seriously deficient groups as regard vitamin D
supplementation, sun exposure and PELOD score. And also there was
significant negative correlation between vitamin D level and PELOD score.
Adequate (>75nmol/L)
Insufficient (30-75nmol/L)
Seriously deficient (<30nmol/L)
87.5
84.6
100
52.6
47.4 12.5
15.4
50
Seriously deficient (<30nmol/L)
Insufficient (30-75nmol/L)
Adequate (>75nmol/L)
0
No
Yes
Adequate (>75nmol/L)
Insufficient (30-75nmol/L)
Figure (3):
Comparison
between three
groups as regard sun
exposure.
Seriously deficient (<30nmol/L)
100
62.5
57.9
50
Figure (2):
Comparison between
three groups as
regard vitamin D
supplementation.
23.1
46.2
31.2
15.8
26.330.8
6.2
0
25OH vitamin D ad
Good
Improper
No
450
400
350
300
250
200
150
100
50
0
Figure (4):
Shows significant
negative correlation
between vitamin D
level and PELOD
score.
0
5
10
15
20
PELOD
25
30
35
Table (3): Vitamin D supplementation and Sun exposure in cases:
Mean
SD
Vitamin D
supplementation
No
Yes
61.89
72.50
169.68
107.60
Sun exposure
Good
Improper
139.48
90.630
76.01
110.133
No
59.68
56.312
p-value
<0.001
>0.05
As regard vitamin D supplementation there was high significant difference
between patients with vitamin D supplementation and patients without,
while there is no significant difference as regard sun exposure.
Table (4) Comparison between vit D on admission and vit D on discharge in discharged
cases
Median
Vit D on admission 63.7
Minimum Maximum
Mean
1
97.5
388
p-value
<0.001
Vit D on discharge 59.1
1
335
94.8
This table shows that there was statistically highly significant difference of
vitamin D level at the time of admission and discharge.
Discussion:
In the current study, 25(OH)D mean level is 91.1 nmol/L , median
level is 63.7 nmol/L, maximum is 388.4 nmol/L and minimum is 1 nmol/L. In
a study by Ripple et al. (9) in Australia the median 25(OH)D level was 56.5
nmol/L.While the mean 25(OH)D was 43.2nmol/L in a study in Canadian
PICU children (2). In another study in north American PICU, the median
25(OH)D was 22.5ng/ml (56.25nmol/L as 1 ng/ml=2.5 nmol/L) (10).
In this study the median patient age was 1 year, and there is an
inverse correlation between 25(OH)D levels and age (r: -0.15). The median
age groups were 2.25 for the seriously deficient, 0.67 for the deficient and
1.1 for the sufficient (p- value<0.05). This goes in agreement with Madden
et al. (10) who found that vitamin D level was lower in the older age group.
In another study the incidence of vitamin D deficiency was compared
between healthy and PICU children in different age groups. As expected,
incidence of vitamin D deficiency increased with age in both group of
patients. PICU patients had double the incidence of hypovitaminosis D in all
age groups, but the differences were clearly statistically significant in the
older age group, and were significant in the medium age group (r: -0.421; p
< 0.001) (11).
Lack of vitamin D supplementation and sun exposure are strongly
related to vitamin D deficiency. The present study shows that 87.5% of
severely deficient group and 84.6% of insufficient group were not taking
vitamin D supplementation. We noticed that 93.7% of severely deficient
and 77% of insufficient were with improper or no exposure to sun. This
explains
the
positive
correlation
between
25(OH)D,
vitamin
D
supplementation and sun exposure (p-value<0.05). Similar to our results,
Madden et al. (10) found the same relation as 58.3% were not taking
neither vitamin D nor other multivitamins (p-value <0.0001) and noted that
vitamin D supplementation before PICU admission was strongly protective
against 25(OH)D deficiency.
PELOD score showed higher scores with severely vitamin D deficient
patients which explain the strong negative correlation between vitamin D
level and PELOD score (r: -0.3; p <0.05) ;while the number of organ system
failure were not related to vitamin D deficiency. While no other studies
studied the relation between PELOD score and 25(OH)D, McNally et al. (2)
only used PELOD score to define hepatic dysfunction. It is possible that
25(OH)D deficiency amplifies the metabolic derangements and impaired
immune regulation seen in critically ill states, which may lead to worse
outcomes than would be experienced with normal vitamin D levels (12).
This study included 19 (39.6%) ventilated patients out of 48 patients,
42.1% of vitamin D sufficient, 46.2% of deficient and 31.2% of seriously
deficient were ventilated patients. On the other hand, mechanically
ventilated patients represent in McNally et al. (2) 65% of vitamin D
sufficient group and 75% of vitamin D deficient. In Rippel et al., (9) 98.4% of
vitamin D sufficient group and 97.7% of vitamin D deficient group of post
operative cardiac surgical patients, 82.7% of vitamin D sufficient group and
75% of vitamin D deficient group of the general medical intensive care
population and in Rey et al. (11) 40.9% of vitamin D sufficient group and
39.1% of vitamin D deficient group. All previous studies including our study
found no relation between mechanical ventilation and vitamin D deficiency.
We measured vitamin D at the time of discharge in survived cases (35
cases); there was high significant difference between the level of vitamin D
on admission and its level on discharge as the median of vitamin D level of
these cases on admission 63.7 nmol/L and on discharge was 59.1 nmol/L (p
value < 0.001). While no other studies studied the level of vitamin D at the
time of discharge.
Conclusions
The incidence of vitamin D deficiency was found to be high in
critically ill pediatric patients admitted to Benha University Hospitals.
Deficiency of vitamin D was found related to increasing age, lack of vitamin
D supplementation and lack of sun exposure.
There significant decrease in vitamin D level at the time of PICU
discharge when compared with its level on admission.
Mortality in PICU is affected with many risk factors like: PRISM III
score, CV SOFA score, sepsis and sun exposure.
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